New Guidelines for the Management of Aspergillosis

Nicola M. Parry, DVM

July 05, 2016

Early diagnosis and treatment of the major forms of aspergillosis are the focus of a new practice guideline from the Infectious Diseases Society of America (IDSA).

The evidence-based recommendations highlight data from clinical studies that evaluated new and current therapies for the management of Aspergillus infection, as well as data on the use of non-culture-based biomarkers for diagnosing infection. In particular, the guidelines focus on the management of the major forms of aspergillosis (allergic, chronic, and invasive), with special emphasis on invasive aspergillosis because it remains a significant cause of morbidity and mortality in high-risk, immunocompromised patients.

Thomas F. Patterson, MD, from the University of Texas Health Science Center at San Antonio, and colleagues published the updated practice guideline online June 29 in Clinical Infectious Diseases.

"This document constitutes the guidelines of [IDSA] for treatment of aspergillosis and replaces the practice guidelines for Aspergillus published in 2008," the authors write. However, they emphasize that guidelines cannot always account for individual patient variation, and are therefore not intended to replace physicians' clinical judgment.

The authors emphasize that improved use of diagnostic tools has increased clinicians' ability to make an early diagnosis of aspergillosis. Until molecular diagnostic techniques become more widely used in clinical laboratories, the guidelines recommend submission of tissue and fluid specimens for histopathologic, cytologic, and culture examination to diagnose invasive aspergillosis. However, molecular techniques, such as DNA sequencing, should be used to identify Aspergillus species in cases that involve either isolates with atypical growth or concern for resistance.

If invasive pulmonary aspergillosis (IPA) is suspected in a patient, the guidelines recommend performing computed tomography scanning of the chest, regardless of chest radiography findings. Bronchoscopy with bronchoalveolar lavage is also recommended in these patients, unless significant comorbidities (such as bleeding or severe hypoxemia) preclude it.

Detection of galactomannan (a component of the Aspergillus cell wall) in serum or bronchoalveolar lavage fluid is recommended as an accurate marker for the diagnosis of invasive aspergillosis in adults and children, when used in certain patient subpopulations, such as hematopoietic stem cell transplant recipients or patients with hematologic malignancies.

The guidelines also discuss emerging diagnostic tools with the ability to further improve the early diagnosis of Aspergillus infection. For instance, Aspergillus polymerase chain reaction (PCR) testing has been shown to be more sensitive than culture in detecting the fungus in blood and respiratory fluids. Nevertheless, although a promising diagnostic tool, these assays have not been standardized and validated for routine clinical use, and the role of PCR testing in patient management remains unclear. Clinicians should therefore consider the use of Aspergillus PCR on a case-by-case basis.

The availability of antifungal agents that are more active, better tolerated, and/or developed in extended-release formulations has also substantially improved therapy for patients at risk for serious Aspergillus infections, the authors note.

If IPA is suspected, antifungal therapy should be initiated while diagnostic evaluation is ongoing. Voriconazole is recommended for primary treatment of IPA, although combination therapy with voriconazole and echinocandin may be warranted for some high-risk patients. Antifungal therapy for IPA should continue for at least 6 to 12 weeks. Antifungal prophylaxis should also be instituted for patients with prolonged neutropenia who are at high risk for IA. Prophylactic regimens with posaconazole, voriconazole, and/or micafungin are considered to be most effective.

The guidelines do not recommend routine testing for antifungal susceptibility testing. Instead, it should be reserved for cases in which infection with an azole-resistant isolate is suspected, or in which a patient is unresponsive to antifungal agents.

The guideline, which has also been endorsed by the Pediatric Infectious Diseases Society, recommends using the same antifungal agents for treatment of aspergillosis in children as are used in adults. However, dosing of many of these agents may be different for children. The authors also note that although voriconazole is only approved by the US Food and Drug Administration for children aged 12 years and older, it is the cornerstone of aspergillosis treatment in children of all ages.

Yet, despite recent advances, the authors acknowledge that development of new antifungal agents is still needed for effective management of aspergillosis, because "even with optimal antifungal therapy the mortality rate remains high."

They conclude, "Critical gaps in knowledge remain regarding management of these infections including the optimal utility of combination therapy, tools for early detection of these infections, evaluation of response, therapy for patients with breakthrough or refractory infection, and the population of patients for whom prophylaxis would be most beneficial."

Several coauthors have received funding from the National Institute for Health Research, Medical Research Council, Global Action Fund for Fungal Infections, the Fungal Infection Trust, Alsace contre le Cancer, Pfizer, and the National Institutes of Health. Several coauthors have reported various financial relationships with various companies: Astellas, Merck, Revolution Medicines, Amplyx, Durata, Cidara Therapeutics, Gilead, Pfizer, Scynexis, Toyama, Vical, Viamet, F2G Ltd, Novocyt, Sigma Tau, Basilea, Pulmocide, Dynamiker, T2 Biosystems, F2G Inc, Celgene, Amgen, GSK, Genentech, ViraCor, Assembly Biosciences, Novartis, and Methlygene. One coauthor has a patent: US No. 13/511 264.

Clin Infec Dis. Published online June 29, 2016. Full text

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